Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients
This study aimed to assess the naturally occurring variation in plasma fatty acids in healthy subjects and Parkinson’s disease (PD) patients. Alpha-synuclein (aSyn) plays a major role in Parkinson’s disease. Inhibition of stearoyl-CoA desaturase (SCD) reduces levels of mono-unsaturated C16 and C18 f...
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| Format: | Article |
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Elsevier
2025-12-01
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| Series: | Biomarkers in Neuropsychiatry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666144625000140 |
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| author | Pepijn P.N.M. Eijsvogel Andriy A. Gorbenko Dan F. Tardiff Michelle Skupien Ken Rhodes Robert H. Scannevin Yalcin Yavuz Emilie M.J. van Brummelen Brigitte Robertson Philip H.C. Kremer Geert Jan Groeneveld |
| author_facet | Pepijn P.N.M. Eijsvogel Andriy A. Gorbenko Dan F. Tardiff Michelle Skupien Ken Rhodes Robert H. Scannevin Yalcin Yavuz Emilie M.J. van Brummelen Brigitte Robertson Philip H.C. Kremer Geert Jan Groeneveld |
| author_sort | Pepijn P.N.M. Eijsvogel |
| collection | DOAJ |
| description | This study aimed to assess the naturally occurring variation in plasma fatty acids in healthy subjects and Parkinson’s disease (PD) patients. Alpha-synuclein (aSyn) plays a major role in Parkinson’s disease. Inhibition of stearoyl-CoA desaturase (SCD) reduces levels of mono-unsaturated C16 and C18 fatty acids, which are involved in aSyn toxicity in vitro and in vivo. The ratio of mono-unsaturated to saturated fatty acids (fatty acid desaturase index (FA-DI)) in plasma after SCD-inhibition correlates with effects on brain FA-DI. However, the FA-DI normal values and the inter- and intra-day variation in PD-patients and healthy subjects is unknown. Ten PD-patients (54 –73 years) and ten age-matched healthy subjects were included. On three consecutive days, fatty acids fractions and concentrations were measured throughout the day. Outcomes are expressed as estimated mean, and the coefficient of variation (CV%) in percentage. For C16 FA-DI, the inter-subject CV% was 20.7 % in healthy subjects, and 37.7 % in PD-patients. The intra-subject CV% over days was 14.0 % in healthy subjects, and 14.2 % in PD-patients, and within days 5.1 % in healthy subjects, and 5.9 % in PD-patients. For C18 FA-DI, the inter-subject CV% was 14.8 % in healthy subjects, and 16.0 % in PD-patients. The intra-subject CV% over days was 11.0 % in healthy subjects, and 8.6 % in PD-patients, and within days 8.4 % in healthy subjects, and 6.7 % in PD-patients. The observed extent of variability in healthy subjects and PD-patients support C16 and C18 FA-DI as suitable biomarkers to demonstrate target engagement in plasma, of for example SCD-inhibitors, in both healthy subjects and PD-patients. |
| format | Article |
| id | doaj-art-e9a1b1dd53d748db85c5c6417a078784 |
| institution | OA Journals |
| issn | 2666-1446 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomarkers in Neuropsychiatry |
| spelling | doaj-art-e9a1b1dd53d748db85c5c6417a0787842025-08-20T02:35:19ZengElsevierBiomarkers in Neuropsychiatry2666-14462025-12-011310013210.1016/j.bionps.2025.100132Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patientsPepijn P.N.M. Eijsvogel0Andriy A. Gorbenko1Dan F. Tardiff2Michelle Skupien3Ken Rhodes4Robert H. Scannevin5Yalcin Yavuz6Emilie M.J. van Brummelen7Brigitte Robertson8Philip H.C. Kremer9Geert Jan Groeneveld10Centre for Human Drug Research, Zernikedreef 8, Leiden 2333 CL, the Netherlands; Leiden University Medical Centre, Albinusdreef 2, Leiden 2333 ZA, the Netherlands; Corresponding author at: Centre for Human Drug Research, Zernikedreef 8, Leiden 2333 CL, the Netherlands.Centre for Human Drug Research, Zernikedreef 8, Leiden 2333 CL, the Netherlands; Leiden University Medical Centre, Albinusdreef 2, Leiden 2333 ZA, the NetherlandsCAMP4 Therapeutics, 1 Kendall Square, Building 1400 West, 3rd Floor, Cambridge, MA 02139, United StatesWalden Biosciences, 1 Kendall Square, Suite 7102, Cambridge, MA 02139, United StatesBristol Myers Squibb, 250 Water Street, Cambridge, MA 02141, United StatesVerge Genomics, 131 Oyster Point Blvd, Suite 300, South San Francisco, CA 94080, United StatesCentre for Human Drug Research, Zernikedreef 8, Leiden 2333 CL, the NetherlandsJohnson and Johnson, Einsteinweg 101, Leiden 2333 CB, the NetherlandsAdial Pharmaceuticals, 4870 Sadler Road, Suite 300, Glen Allen, VA 23060, United StatesCentre for Human Drug Research, Zernikedreef 8, Leiden 2333 CL, the Netherlands; Leiden University Medical Centre, Albinusdreef 2, Leiden 2333 ZA, the NetherlandsCentre for Human Drug Research, Zernikedreef 8, Leiden 2333 CL, the Netherlands; Leiden University Medical Centre, Albinusdreef 2, Leiden 2333 ZA, the NetherlandsThis study aimed to assess the naturally occurring variation in plasma fatty acids in healthy subjects and Parkinson’s disease (PD) patients. Alpha-synuclein (aSyn) plays a major role in Parkinson’s disease. Inhibition of stearoyl-CoA desaturase (SCD) reduces levels of mono-unsaturated C16 and C18 fatty acids, which are involved in aSyn toxicity in vitro and in vivo. The ratio of mono-unsaturated to saturated fatty acids (fatty acid desaturase index (FA-DI)) in plasma after SCD-inhibition correlates with effects on brain FA-DI. However, the FA-DI normal values and the inter- and intra-day variation in PD-patients and healthy subjects is unknown. Ten PD-patients (54 –73 years) and ten age-matched healthy subjects were included. On three consecutive days, fatty acids fractions and concentrations were measured throughout the day. Outcomes are expressed as estimated mean, and the coefficient of variation (CV%) in percentage. For C16 FA-DI, the inter-subject CV% was 20.7 % in healthy subjects, and 37.7 % in PD-patients. The intra-subject CV% over days was 14.0 % in healthy subjects, and 14.2 % in PD-patients, and within days 5.1 % in healthy subjects, and 5.9 % in PD-patients. For C18 FA-DI, the inter-subject CV% was 14.8 % in healthy subjects, and 16.0 % in PD-patients. The intra-subject CV% over days was 11.0 % in healthy subjects, and 8.6 % in PD-patients, and within days 8.4 % in healthy subjects, and 6.7 % in PD-patients. The observed extent of variability in healthy subjects and PD-patients support C16 and C18 FA-DI as suitable biomarkers to demonstrate target engagement in plasma, of for example SCD-inhibitors, in both healthy subjects and PD-patients.http://www.sciencedirect.com/science/article/pii/S2666144625000140Parkinson diseaseStearoyl-CoA desaturaseFatty acids |
| spellingShingle | Pepijn P.N.M. Eijsvogel Andriy A. Gorbenko Dan F. Tardiff Michelle Skupien Ken Rhodes Robert H. Scannevin Yalcin Yavuz Emilie M.J. van Brummelen Brigitte Robertson Philip H.C. Kremer Geert Jan Groeneveld Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients Biomarkers in Neuropsychiatry Parkinson disease Stearoyl-CoA desaturase Fatty acids |
| title | Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients |
| title_full | Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients |
| title_fullStr | Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients |
| title_full_unstemmed | Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients |
| title_short | Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients |
| title_sort | fatty acids as potential biomarkers of stearoyl coa desaturase inhibition variation in healthy subjects and parkinson s disease patients |
| topic | Parkinson disease Stearoyl-CoA desaturase Fatty acids |
| url | http://www.sciencedirect.com/science/article/pii/S2666144625000140 |
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